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Aim: To examine the incidence of with first‐episode psychosis (FEP) in the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, and to examine the association between the Duration of Untreated Psychosis (DUP) and the clinical course. Methods: Participants recruited in 2013–2019 were assessed with the Health of the Nation Outcome Scale (HoNOS) every 6 months for 24 months. Hierarchical growth models analysed changes of global severity (HoNOS total scores) and symptom dimensions. Regression modelled factors associated with remission (HoNOS < 8) and clinical improvement (<12). Results: The incidence of FEP was 21.5 (95%CI: 21.2–21.9) cases per 100 000 person year. Among participants (n = 86, mean age 23, 76% males), baseline HoNOS scores were higher for those with a longer DUP. More than half subjects reached clinical remission (61.6%) or improvement (82.6%), while very few (2.3%) were re‐hospitalized. HoNOS total scores decayed with a mixed linear/quadratic trend, with a slower decay among migrants. A longer DUP was associated with reduced improvements of positive symptoms and lower likelihood of clinical improvement (OR: 0.84; 95%CI: 0.73–0.96). Conclusions: Patients from the FEP program of Ferrara reached good clinical outcomes. Nonetheless, individuals with a longer DUP may need additional clinical attention. Systematic monitoring of clinical outcomes may be an optimal strategy to improve the outcomes of FEP in the real world. [ABSTRACT FROM AUTHOR]